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ICCS S2: LUT DYSFUNCTION (CONT.)
Moderators: Israel Franco (USA) & Anka Nieuwhof-Leppink (Netherlands)
ICCS Meeting on Thursday 15, October 2015, 16:10 - 16:40
16:10 - 16:16
ICCS S2-1
(LO)
YOUNG RATS EXHIBIT AN AGE AND SEX DEPENDENT BLADDER RESPONSE TO
ALPHA ANTAGONISTS BUT NOT BETA AGONISTS
Hsi-Yang WU and China CHIEN
Stanford University, Urology, Palo Alto, USA
PURPOSE
The use of alpha-1 antagonists for dysfunctional voiding and beta-3 agonists for overactive bladder in children will likely
increase over time. We studied the response of the rat bladder and external urethral sphincter (EUS) after birth to
determine if there was an age during which these compounds become effective, since previous studies showed a
delayed onset of alpha receptor activity until 6 weeks of life.
MATERIAL AND METHODS
Sprague-Dawley rats underwent cystometry and EUS electromyography under urethane anesthesia at ages 3 weeks
(weaning), 6 weeks (puberty), and 9 weeks (young adult). 6 females and 6 males were studied at each time
point. Maximum intravesical pressure during voiding, pressure threshold, bladder capacity, EUS storage and emptying
function were measured. The non-selective alpha agonist phenylephrine (0.3 mg/kg), alpha antagonist phentolamine
(1-3 mg/kg), beta agonist isoprenaline (3 mg/kg), and beta antagonist propranolol (3 mg/kg) were injected
intravenously.
RESULTS
The alpha antagonist phentolamine lowered intravesical pressure in 6 and 9 week old males and 6 week old females, but
did not lower the pressure threshold. The beta agonist isoprenaline lowered intravesical pressure in males and females
of all ages, also without affecting the pressure threshold. The pressure threshold in males and females of all ages was
increased by the beta antagonist propranolol, which also decreased bladder capacity in females. Neither the alpha
antagonist nor the beta agonist improved bladder capacity or EUS storage and emptying function.
CONCLUSIONS
Alpha antagonists are more effective at lowering intravesical pressure in post-pubertal male rats than in female
rats. Beta agonists reliably lower intravesical pressure in male and female rats of all ages. We propose that alpha
antagonists be used in older males, and beta-3 agonists be used in females and younger males, if the beta-3 agonists
are shown to be safe in children.